This project will consist of a detailed analysis of the effect of complement (C) components of the classical pathway on selected physicochemical and biologic properties of model soluble immune complexes (model ICx). Model ICx will consist of stable heat-aggregates and crosslinked oligomers of human IgG (and its subclasses) IgM, F(ab')2 and BSA (control). Different-size model ICx will be reacted sequentially with purified C1, C4, C2 and C3 in various doses in order to determine (1) the effect of incorporation of differing quantities of these C components upon the activation and incorporation of each other and (2) the effect of each component on the size and charge of model ICx. Normal serum, C2 and C5 deficient serulm and serum depleted of various C components will also serve as sources of C for reaction with model ICx. Model Icx containing C1, C4 and/or C3 will also be reacted with isolated human monocytes and mouse macrophages in order to study the effect of these C components on the binding, pinocytosis and catabolism of model ICx by mononuclear phagocytes. By these studies we hope to elucidate how the interaction of soluble ICx with C affects properties of ICx that are likely to be important in determining their pathogenic potential.